Transplantation of human neural precursor cells in the 6-OHDA lesioned rats: Effect of immunosuppression with cyclosporine A

Schwarz, Sigrid C.; Wittlinger, Jan; Schober, R.; Storch, Alexander; Schwarz, Johannes

doi:10.1016/j.parkreldis.2006.01.003

Cited by 35 publications

(32 citation statements)

References 29 publications

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“…These studies further demonstrated that implantation of precursor-derived dopaminergic neurons from rodents leads to histological, biochemical and functional recovery in animal models of PD [85,99,105,107,108], but only recent studies used NSCs after long-term expansion [94]. After the reports on long-term expansion and functional dopaminergic differentiation of human midbrain NSCs [77,87,95,96], we were able to demonstrate functional and histological reconstitution after transplanting these cells into the striatum of parkinsonian rats [84]. Moreover, we found only mild immunoreactions and no tumor formation.…”

Section: Fetal Neural Stem Cellsmentioning

confidence: 82%

“…Most in vitro studies regarding fetal midbrain NSCs involved rodent embryos at embryonic day (E)14 to E15 [65,76,80,82], while on human midbrain material, samples of 6-9 weeks post-fertilization were used [77,[83][84][85][86][87]. Gensburger and co-workers (1987) found that fibroblast growth factor-2 (FGF-2) could induce proliferation of neural precursors in embryonic hippocampal cultures initiating a new field of cell culture experiments studying proliferation of neural precursors in vitro [88].…”

Section: Fetal Neural Stem Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Restorative approaches in Parkinson's Disease: Which cell type wins the race?

Meyer

Maisel

Hermann

et al. 2010

Journal of the Neurological Sciences

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Section: Fetal Neural Stem Cellsmentioning

confidence: 82%

Section: Fetal Neural Stem Cellsmentioning

confidence: 99%

Restorative approaches in Parkinson's Disease: Which cell type wins the race?

Meyer

Maisel

Hermann

et al. 2010

Journal of the Neurological Sciences

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“…Although cyclosporine was the first calcineurin inhibitor that revolutionized immunosuppression by strongly reducing the rate of rejection in solid organ transplantation and still remains very effective, it is currently supplanted by tacrolimus. Previous data have suggested that cyclosporine could be deleterious in the maturation process of NPC [6,7], when other publications suggest that cyclosprorine could be beneficial [8,9]. Most of the published data have concluded that cycloporine had direct effect on neuron differentiation, but protected the engrafted cells from rejection [8,9].…”

Section: Discussionmentioning

confidence: 99%

The Role of Immunosuppression in the Transplantation of Allogenic Neural Precursors Derived from Human Pluripotent Stem Cells for Parkinson’s Disease

Rham¹,

Tieng²,

Tournier³

et al. 2013

J Stem Cell Res Ther

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Objective: Neural progenitor cells (NPC) derived from human embryonic stem cells have the potential to differentiate into mature neurons after transplantation in the brain, opening the possibility of regenerative cell therapy for neurodegenerative disorders like Parkinson's disease. For such therapy, the source of NPC is genetically unrelated to the patient, leading to potential rejection of the transplanted cells by the host's immune response. Rejection can be prevented by the use of immunosuppressive drugs (ISD). Previous works have suggested that cyclosporine and dexamethasone used in classical immunosuppressive regimen could prevent the terminal differentiation of NPC into mature neurons depending on culture conditions. Methods:We have investigated in vitro the role of other ISD, Intra venous Immunoglobulins (IvIG), mycophenolate mofetil and tacrolimus. We have tested the immunosuppressive activity of tacrolimus and cyclosporine on the effector of natural killer (NK) and CD8 + T-cells and performed a microarray to analyse the difference between the two drugs for the neuron differentiation. Finally, human transplanted neuroprecursor cell survival has been analyzed in rats treated with tacrolimus or cyclosporine and anti-inflammatory treatments.Results: IvIG and mycophenolate mofetil interfere with the development of NPC into mature neurons, but tacrolimus do not inhibit the maturation process of NPC. Microarray experiments demonstrate significant differences between cyclosporine and tacrolimus gene expression during NPC maturation into mature neurons. Tacrolimus like cyclosporine is able to inhibit the CD8 + T-cells activation against neural progenitors, but both are unable to block NK cells activity. NK cells could be potential harmful weapons to reject NPC and mature neurons. In rats treated with both immunosuppressive (tacrolimus or cyclosporine) and anti-inflammatory treatments, engrafted human neuroprecursors cell survival is good and the microglial density is low. Conclusion:These data suggest in vivo that both tacrolimus and cyclosporine, with an anti-inflammatory treatment like prednisolone, promote graft survival and minimise the host microglial response.

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“…The effect of various cell sources have been investigated in animal models of PD, as well as in humans, and these include, embryonic stem (ES) cells (Freed et al, 2001;Kim et al, 2002, see Lindvall and, induced pluripotent stem (iPS) cells (Wernig et al, 2008), fetal and adult brain-derived neural stem cells (NSC; Hermann et al, 2006;Schwarz et al, 2006), mesenchymal stem cells (MSC; Hellmann et al, 2006;Cova et al, 2010), and amniotic fluid stem (AFS) cells (Donaldson et al, 2009). In an interesting application of regenerative pharmacology, neural progenitors generated from pluripotent stem cells in culture were induced to give rise to dopaminergic neurons, which hold therapeutic potential for PD.…”

Section: B Parkinson's Diseasementioning

confidence: 99%